Dr. Conklin and his group use high-throughput gene function studies to identify new genes and elucidate molecular pathways important to human cancer cells. Cancer therapies strive to selectively eliminate tumor cells while having no effect on normal cells. Unfortunately, most current therapies fail to reach this goal because their limited specificity often targets any rapidly proliferating cell in the body rather than actual tumor cells. The genetic alterations in cancer cells that contribute to tumorigenesis and alter treatment response, often create molecular vulnerabilities –Achille’s heels -that can be targeted therapeutically. Using approaches that directly identify genes critical to tumor cell survival, his lab has found a number of new genes related to altered signaling and metabolism in breast cancer.
The group has shown that inhibiting the lipogenic pathway kills HER2/neu-positive breast cancer cells and prevents tumor initiation in vivo. Current work seeks to understand how tumor cells communicate with normal cells using metabolites and to understand why tumors that express high levels of some proteins involved in lipid synthesis, storage and trafficking are associated with a poorer prognosis.
The Conklin group has also identified a novel isoform of the B-cell kinase, BTK, as an attractive solid tumor drug target. The isoform, BTK-C, is expressed from an alternative transcriptional start site in approximately 40% of several solid tumor types including breast, prostate, ovarian and lung. Down-regulation of BTK-C with RNAi or inhibition with pharmacological inhibitors has a number of desirable anticancer effects including inducing apoptosis, preventing the onset of drug resistance and decreasing bone metastases in vivo.
- Functional genomics
- Cancer cell metabolism
- Cancer cell signaling